This application is for the renewal of grant 5T32CA00911038 to support the training of predoctoral students and postdoctoral fellows in the fundamental biochemical, molecular, and cellular processes that ultimately give rise to the alterations characteristic of neoplastic transformation. Training is provided primarily by faculty from the Department of Biochemistry and Molecular Biology of the Johns Hopkins Bloomberg School of Public Health and the Sidney Kimmel Comprehensive Cancer Center of the Johns Hopkins Medical Institutions. The recruitment of nineteen new faculty members in recent years, the implementation of major revisions to the curriculum, and the introduction of individualized development plans will provide all trainees continued access to cutting edge instruction and research training opportunities in wellfunded and productive laboratories, and the knowledge to respond to the new and rapidly evolving research environment. Going forward, the Program requests support for seven predoctoral and three postdoctoral trainees per year. Trainees are required to attend and participate in a cancerfocused seminar series, a weekly journal club, a monthly research colloquium and related events that enhance their reasoning skills as bench scientists, their oral and written presentation skills, and their ability to work in a team settingand eventually lead. Predoctoral trainees are admitted to the Program after they have demonstrated a strong academic and laboratory rotation record in their first year of training and have selected a thesis dissertation project with a clear relevance to cancer. Outstanding postdoctoral candidates with a strong and substantiated interest in the pursuit of cancer biology are recruited to this Program. Major research themes with relevance to the cancer problem include: cell division, cell differentiation, and cell death; cellular remodeling and associated regulatory circuits; transcriptional, post-transcriptional and epigenetic regulation of gene expression; chromosomes, genome biology and maintenance of genome integrity; protein quality control mechanisms; stem cell biology and the role of microenvironments; inflammation and immune responses? chemical biology; and biomarkers. In the past this program has attracted talented young trainees, most of whom have remained in science and many of whom have achieved distinction in cancer biology. The proposed program will continue to bring trainees into the field and equip them for productive careers in cancer research.